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All Hands on Deck

Fighting Parkinson's disease

Jason Cannon, assistant professor of health sciences, examines the role of dietary and environmental factors on the development of Parkinson’s disease.

Parkinson’s disease is the second most common neurodegenerative disease, after Alzheimer’s, in the United States. A disorder that affects movement and cognition, it was largely unknown to most Americans until boxer Muhammad Ali and actor Michael J. Fox put a face to the disease.

Nearly 1 million people in the U.S. are living with Parkinson’s disease while still others suffer from Parkinsonian syndrome — conditions that have the symptoms of Parkinson’s disease, such as tremors, stooped posture, slowness and shuffling gait. With the nation’s aging population, the numbers are expected to grow.

Some researchers in the College of Health and Human Sciences (HH S) are examining the role of environmental exposures to better understand the effect on the neural system and mechanisms of Parkinson’s while others at Purdue are working to improve the lives of those living with the debilitating disease.

Revealing Toxic Exposure

Since British physician James Parkinson first described the “shaking palsy” in 1817, Parkinson’s disease has been linked to a variety of possible environmental causes, both natural and artificial.

According to research reported in Archives of Neurology (Sept. 2009), individuals whose occupation involves contact with pesticides appear to have an increased risk of developing Parkinson’s disease.

He joined the faculty in the School of Health Sciences in January and is setting up a laboratory where he and his research assistants will test the role of dietary and environmental factors on the development of the disease.

Cannon’s Purdue research is funded by a career development award from the National Institutes of Health (NIH) and focuses on the development of new models using compounds that have been linked to Parkinson’s disease. These newly developed models are used to test interactions between environmental and genetic factors and also to test potential treatments.

“Only about 10 percent of Parkinson’s disease cases can be directly linked to inheritance,” Cannon says. His prior postdoctoral research focused on both environmentally relevant toxins and genetics.

Researchers suggest that the disease is probably a combined result of having a genetic predisposition to the disease and exposure to some sort of neurotoxin. Many people in the field express this as “genetics loads the gun and environment pulls the trigger.”

Although the exact origins of the disease remain to be found, Cannon and his team hope to identify multifactorial causes, examining the critical role of environmental factors, such as pesticides like rotenone, that may act on genetically predisposed individuals. He also is developing a new graduate course titled Analytical Toxicology and Pathology.

Ulrike Dydak, associate professor of health sciences, specializes in medical imaging of neurodegenerative diseases, studying people with jobs like welding.

Welding exposes workers to manganese and there is no clear way to tell at present who might develop Parkinsonian symptoms. Of course, not all welders will develop the disease but researchers hope to identify specific markers that warn of that possibility if a certain threshold is passed.

Several others, including Neil Zimmerman, associate professor of industrial hygiene, and Wei Zheng, head of the School of Health Sciences, have studied neurotoxicology of manganese in populations of welders in Italy and China.

Through her NIH grant, Dydak’s team has studied welders in China, where exposure levels to manganese are greater.

“We were surprised to find elevated brain GABA levels in young Chinese welders who haven’t been exposed to manganese that long or at high levels and who aren’t exhibiting symptoms,” Dydak says. GABA (gamma-aminobutyric acid) is an inhibitory neurotransmitter in the brain that prevents over-firing of the nerve cells.

“We need to find out the specificity of this finding. The GABA level itself may not be specific to Parkinson’s disease, but could serve as a biomarker that needs to be watched,” Dydak says.

Through a new $2 million NIH grant, Dydak will expand her research to follow welders at a local manufacturing company and a Chinese cohort over a five-year period. Her team will assess other types of exposure markers from the air, blood and nail clippings and measure GABA, neurotransmitters and 15 other metabolites in the brain.

“One is N-acetylaspartate (NAA), a metabolite that indicates how well neuronal cells are working in the brain,” Dydak says. For example, if the density level of neurons goes down or dies, this marker goes down as well. This occurs in many diseases like Alzheimer’s and Parkinson’s. “We have found this happening in the frontal cortex of welders.”

Manganese creates a bright signal seen on MRIs that show areas where it has been deposited in the brain.

The best-case scenario, Dydak says, is that the study will find a clear biomarker that shows when someone is at risk for developing Parkinsonian symptoms.

“It’s about understanding the mechanism and differences between idiopathic Parkinson’s disease and manganese toxicity, which should help with treatment,” Dydak says. “If we understand where in the brain things are different, then we can understand what kinds of drugs should work.”

Julia Chester, associate professor of psychological sciences, is looking for mechanisms that can be targeted with drugs to help alleviate some of the motor dysfunctions associated with Parkinson’s and other neurodiseases.

Chester says current drug therapies for Parkinson’s aren’t very effective. “And they tend to become more ineffective over time. We’re still working on the dopamine mechanism but in more selective ways to avoid some of the side effect issues.”

Dopamine agonists directly stimulate the receptors in nerves in the areas of the brain where dopamine-generating cells have been destroyed by the disease. Agonists, chemicals that bind to a receptor of a cell, often mimic the action of a naturally occurring substance.

“This is very exciting work for me,” Chester says. “We’re on the forefront of new discoveries and better drug treatments.”

Living with Parkinson’s

While these HH S researchers search for Parkinson’s causes, other faculty research is leading to improvement in the quality of life for those stricken with the disease.

Jessica Huber, associate professor of speech, language, and hearing sciences, teamed with Jeffrey Haddad, assistant professor of health and kinesiology, on a study that looked at the ability of patients with Parkinson’s disease to balance and talk.

“People with Parkinson’s are more apt to fall because walking, standing and talking are all very cognitively demanding,” Haddad says. Neural circuits between the basal ganglia and the frontal lobe are responsible for the ability to do more than one thing at a time. These areas are impaired in patients with Parkinson’s disease, and they often have difficulty managing multiple tasks simultaneously.

To examine this problem, Haddad and Huber had individuals with Parkinson’s disease and typical older adults stand on a metal force plate to measure balance. While the subject was standing on the plate, a computer monitor displayed pictures and commands to say certain sentences that varied in language complexity. Haddad says, “We examined how their balance changed when they had to generate more complex speech or memorize things while standing and talking.”

This earlier investigation led to a study collaboration with Shirley Rietdyk, associate professor of health and kinesiology. Her research focuses on the interaction of neural and mechanical systems in mobility, posture and balance.

Rietdyk, Haddad and students conducted a study at University Place, a continuing care retirement community, using a new balance device call the Biodex Balance System. It is similar to the Wii Fit game but the base is unstable, like a wobble board with visual feedback.

“If you want to test someone’s balance, you don’t just have them stand still,” Rietdyk says. “You have to challenge their balance system because people are more likely to fall when they’re moving during everyday activities such as walking, stepping up onto a curb or reaching forward to put something in a cupboard. The risk of instability increases further if they are completing another task at the same time, such as talking to their spouse while carrying a tray of food.”

“IF we understand where in the brain things are different, then we can understand what kinds of drugs should work.”

Ulrike DydakAssociate Professor of Health Sciences

They train people with balance and mobility issues in a difficult task to improve stability in their everyday lives.

Haddad and Rietdyk did a six-week intervention with older adults without Parkinson’s at University Place three times a week for 20 minutes at a time. They assessed the group in the Biomechanics Lab and the Motor Development Lab and found that the benefits of training transferred to Haddad’s manual precision task and to Rietdyk’s mobility task requiring subjects to walk and step over obstacles.

“Even though our training did not include walking or manual precision tasks, the intervention improved their mobility and their balance while reaching forward,” Rietdyk says.

Better Walking and Talking

A new research investigation will study treadmill and Biodex training to improve mobility in patients with Parkinson’s disease and typical older adults.

Though it may sound like an impossible task for those with mobility issues, Haddad says treadmill training helps patients overcome halting or freezing of gait by forcing them to walk because the belt is moving.

Subjects are harnessed for safety. “The treadmill belt pulls the foot backward,” Rietdyk says, “providing an external cue to push them beyond their level of comfort in walking.”

Haddad, Rietdyk and Huber will compare Biodex training to treadmill training to see which is more beneficial and if gains translate to improvement in quality of life.

Rietdyk says one of the most satisfying outcomes of the research has been the involvement of undergraduates in the training. “It was rewarding to see relationships develop between the students and the residents at University Place. The students became much more invested in the research than I’ve seen in other projects.”

In addition to mobility studies, Huber and colleagues in the Purdue Research Park have created a wearable device, the SpeechVive, improving both loudness and clarity of speech in patients with Parkinson’s disease in real-world conversations, not just in a speech therapist’s office.

“People with Parkinson’s disease commonly have voice and speech problems,” Huber says. Because of these difficulties with communication, patients often feel invisible or ignored.

The SpeechVive plays noise, called multitalker babble, which resembles the noisy chatter of a restaurant full of patrons in one of the patient’s ears while he/she is speaking. The noise elicits a reflex called the Lombard effect and the patients talk more loudly and clearly.

This story was authored by Della Pacheco, and appeared in the Fall 2012 issue of College of Health and Human Sciences Life 360 Magazine.